August 24, 2022
2 min read
Williams reports being an inventor on a patent pending related to short-read nanopore sequencing. Please see the study for all other authors’ relevant financial disclosures.
A new genetic testing method may save time and money in the detection of abnormal chromosomes compared with traditional prenatal tests, according to correspondence published in The New England Journal of Medicine.
“Aneuploidy (the problem of having extra or missing chromosomes in the cells of an embryo, fetus or baby) is a catastrophic situation that is, by far, the most common cause of miscarriage and major cause of developmental delays and congenital anomalies,” S. Zev Williams, MD, PhD, the Wendy D. Havens Associate Professor of Women’s Health and chief of the division of reproductive endocrinology and infertility at Columbia University Irving Medical Center (CUIMC) in New York City, told Healio.
“What prompted this study was the realization that existing methods for testing for aneuploidy across all of reproduction — from the earliest embryo produced using IVF to miscarriage samples, chorionic villus samples and amniocentesis samples — had very serious shortcomings: they were too slow, cost too much and required samples be sent to a reference lab,” Williams said. “We realized that if we could develop a new technology that would take hours instead of weeks to give results, that could cost hundreds instead of thousands of dollars to run and that could be done at the point of care instead of sending to a reference lab, this would have major benefits to patients.”
Williams and colleagues termed the resulting technology the short-read transpore rapid karyotyping (STORK) method, which takes 10 minutes and $200 per sample to sequence one sample, or 2 hours and less than $50 per sample to sequence 10 samples simultaneously, according to the correspondence.
“STORK uses nanopores — tiny protein channels arranged on a membrane on a hand-held device — that sequence short strands of DNA as they flow through the cell,” Williams said. “But it does this sequencing 15,000 times faster than traditional sequencing technologies and uses a simple preparation step so that the testing can be done at the clinical site without needing to send the sample to a reference laboratory.”
STORK vs. traditional testing
To assess this technique, Williams and colleagues performed blinded testing of 218 residual reproductive specimens, which included products of conception from spontaneous pregnancy loss, chorionic villi from chorionic villus sampling, amniotic fluid from amniocentesis and trophectoderm biopsy specimens from embryos undergoing preimplantation genetic testing for aneuploidy, according to the correspondence. They compared these test results with those obtained from traditional prenatal tests.
Compared with standard testing, STORK results were 100% accurate for products of conception (95% CI, 94.3%-100%), chorionic villi (95% CI, 93.2%-100%) and amniotic fluid samples (95% CI, 92.9%-100%). STORK and standard testing results were discordant for 10 products of conception samples, but subsequent testing resolved this.
Additionally, the researchers trained laboratory technicians in STORK testing, who then conducted STORK testing for another 60 samples. The results of these tests were 100% concordant with standard testing (95% CI, 80.5%-100%).
Future of STORK
Moving forward, Williams suggested the STORK method be investigated in multi-center clinical trials to validate their findings.
The STORK test is currently awaiting authorization from the New York State Department of Health for use in CUIMC patients, according to a press release.